There are two major factors that should be considered in Near Infrared (NIR) non-invasive measurement of blood analytes. The first factor is the magnitude of the absorbance of NIR radiation by the analyte, referred to as the analyte signal, and the second factor is the location of analyte in the sample body part that is placed in the path of NIR radiation. Assuming that the analyte signal is adequate for non-invasive measurement of same, the main cause of error may lie in the physiology of the body part placed in the path of electromagnetic radiation. Although reference is made herein to the finger, as is the preferred body part, the finger should not be considered limiting in any way.
In an average young male, 18% of the body weight is protein and related substances, 7% is mineral, and 15% is fat. The remaining 60% is water. The water and its constituents are located in three major compartments: vascular compartment, the interstitial compartment, and the intracellular compartment. The vascular compartment contains blood, which comprises about 40% red blood cells and about 60% plasma. The vascular and interstitial compartments are the major contributors to the extracellular compartment. The intracellular component of the body water accounts for about 55% of the body weight and the extracellular component for about 45%. In terms of volume, the average body water is about 42 L: 23 L intracellular, and 19 L extracellular of which 8 L are interstitial and 3 L plasma. Many factors affect these proportions, e.g., height, weight, gender, diseases, and age. Within an individual, these proportions can also be affected by activity level, diet, hormone fluctuations, pharmaceuticals, and body part.
Although glucose is used for illustration, similar rational can be used for any blood analyte. Ingested glucose that is absorbed into the rich blood supply of the gut, is circulated around the other parts of the body. All the blood in circulation traverses the entire circuit of the circulation system an average of once each minute when the body is at rest, and as many as six times a minute when a person becomes extremely active. The capillaries are the smallest blood vessels with walls of a single layer of cells and of a diameter barely large enough for red blood cells to squeeze through. The capillary walls are permeable to small molecules like water and glucose. As the blood passes through the capillaries the glucose and water rapidly diffuse from the vascular into the interstitial compartments, where the glucose concentration in both vascular and interstitial compartments equilibrate. Most body cells (e.g. muscle cells) require insulin for glucose uptake. The glucose that is internalized into the cell is rapidly metabolized to provide energy, leaving a very low concentration of glucose in the intracellular compartment, causing the compartment of highest fluid volume to have the lowest glucose concentration.
When NIR is transmitted through a human finger, or other body part, all the substances in the light path absorb light according to the number of absorbing elements, including analytes, present, and the absorptivity of each element. As absorbance of the NIR is correlated with a concentration of a substance dissolved in water (i.e., mass per unit volume, e.g., milligrams/deciliter or mg/dL), a calibration algorithm may be used to predict concentration values of one or more than one analyte in the body part. In developing a calibration algorithm, if the appropriate reference values are not used, the algorithm may not predict analyte concentrations accurately. In the case of glucose, plasma glucose concentration may be used as the reference value or independent variable for developing a calibration algorithm. This reference value works well provided that there is good correlation between plasma glucose concentration and glucose concentration of a body part, for example the finger. Development of a calibration algorithm is disclosed in U.S. Pat. No. 6,372,503 (which is incorporated herein by reference).
In the case of hemoglobin, it is normally only located within the red blood cells, which are restricted to the vascular compartment. The vascular compartment contains arterial blood and venous blood, which may be considered to exist in two sub-compartments. The technology of pulse oximetry is well known for its ability to overcome some of these fluid compartment issues. Furthermore, since pulse oximetry is usually used to measure oxygen saturation of hemoglobin (approximately, the ratio of oxy-hemoglobin to the sum of oxy-hemoglobin and deoxy-hemoglobin) in arterial blood, pulse oximetry has overcome the challenge of isolating the absorbance by arterial blood, from the rest of the tissue, including venous blood. However, the art of pulse oximetry cannot be applied to non-invasive measurement of blood analyte concentration.
U.S. Pat. No. 5,361,758 discloses non-invasive measurement of blood analytes using NIR. There is no teaching of the effects of different fluid compartments, and how to overcome these effects, on the accuracy of the measurement of blood analytes.
U.S. Pat. No. 5,429,128 discloses a finger receptor for repeatable non-invasive measurement of blood analytes using NIR. There is no teaching of the complexity of fluid compartments, and how these effects on the accuracy of the measurement of blood analytes may be overcome.
U.S. Pat. No. 6,167,290 discloses the use of a vacuum to increase the amount of blood in the light path in order to enhance the Raman signal. Again, there is no teaching of the complexity of fluid compartments, and how to overcome the effects of the different compartments on the accuracy of the measurement of blood analytes.
Although reference is made to absorbance of electromagnetic radiation, it should be understood that reflectance measurement is also within the scope of this invention. The optical measurement, whether it is absorbance or reflectance, is dependent on analyte concentration in all body compartments measured, as well as the changes in the ratio of tissue fluids, which is altered by activity level, diet or hormone fluctuations, which in turn, affects the glucose measurement.
It is an object of the present invention to overcome disadvantages of the prior art. This object is met by a combination of the features of the main claims. The subclaims disclose further advantageous embodiment of the invention.